Regional Gray Matter Volume Research Articles

Multimodal-neuroimaging machine-learning analysis of motor disability in multiple sclerosis.

Motor disability is a dominant and restricting symptom in multiple sclerosis, yet its neuroimaging correlates are not fully understood. We apply statistical and machine learning techniques on multimodal neuroimaging data to discriminate between multiple sclerosis patients and healthy controls and to predict motor disability scores in the patients. We examine the data of sixty-four multiple sclerosis patients and sixty-five controls, who underwent the MRI examination and the evaluation of motor disability scales. The modalities used comprised regional fractional anisotropy, regional grey matter volumes, and functional connectivity. For analysis, we employ two approaches: high-dimensional support vector machines run on features selected by Fisher Score (aiming for maximal classification accuracy), and low-dimensional logistic regression on the principal components of data (aiming for increased interpretability). We apply analogous regression methods to predict symptom severity. While fractional anisotropy provides the classification accuracy of 96.1% and 89.9% with both approaches respectively, including other modalities did not bring further improvement. Concerning the prediction of motor impairment, the low-dimensional approach performed more reliably. The first grey matter volume component was significantly correlated (R = 0.28-0.46, p < 0.05) with most clinical scales. In summary, we identified the relationship between both white and grey matter changes and motor impairment in multiple sclerosis. Furthermore, we were able to achieve the highest classification accuracy based on quantitative MRI measures of tissue integrity between patients and controls yet reported, while also providing a low-dimensional classification approach with comparable results, paving the way to interpretable machine learning models of brain changes in multiple sclerosis.

Older people with severe loneliness have an atrophied thalamus, hippocampus, and entorhinal cortex.

Loneliness has been shown to increase the risk of dementia. However, it is unclear why greater loneliness is associated with greater susceptibility to dementia. Herein, we aimed to examine the morphological characteristics of the brain associated with loneliness in older people concerned about cognitive dysfunction. In this retrospective study, 110 participants (80 with amnestic mild cognitive impairment, and 30 cognitively healthy individuals) were included. Participants were assessed using the revised University of California at Los Angeles (UCLA) loneliness scale and had undergone magnetic resonance imaging. Spearman correlation analysis and Mann-Whitney U tests were used to examine the clinical factors associated with loneliness. Multiple regression was performed to examine the relationship between the revised UCLA loneliness scale score and regional gray matter (GM) volume on voxel-based morphometry. The revised UCLA loneliness scale scores were not significantly correlated with age, sex, or mini-mental state examination (MMSE) scores. Multiple regression using age, sex, MMSE score, and total brain volume as covariates showed negative correlations of the revised UCLA loneliness scale scores with the grey matter volume in regions centered on the bilateral thalamus, left hippocampus and left parahippocampal gyrus, and left entorhinal area. Subjective loneliness was associated with decreased GM volume in the bilateral thalamus, left hippocampus, and left entorhinal cortex of the brain in the older people, thereby providing a morphological basis for the increased risk of dementia associated with greater loneliness.

Regional cortical hypoperfusion and atrophy correlate with striatal dopaminergic loss in Parkinson's disease: a study using arterial spin labeling MR perfusion.

To investigate the relationship of the striatal dopamine transporter density to changes in the gray matter (GM) volume and cerebral perfusion in patients with Parkinson's disease (PD). We evaluated the regional cerebral blood flow (CBF) and GM volume, concurrently measured using arterial spin labeling and T1-weighted magnetic resonance imaging, respectively, as well as the striatal specific binding ratio (SBR) in 123I-N-ω-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl)nortropane (123I-FP-CIT) single-photon emission computed tomography in 30 non-demented patients with PD (15 men and 15 women; mean age, 67.2 ± 8.8years; mean Hoehn-Yahr stage, 2.2 ± 0.9). Voxel-wise regression analyses using statistical parametric mapping (SPM) were performed to explore the brain regions that showed correlations of the striatal SBR to the GM volume and CBF, respectively, with a height threshold of p < 0.0005 at the voxel level and p < 0.05 family-wise error-corrected at the cluster level. SPM analysis showed a significant positive correlation between the SBR and GM volume in the inferior frontal gyrus (IFG). Whereas, a positive correlation between the SBR and CBF was widely found in the frontotemporal and parietotemporal regions, including the IFG. Notably, the opercular part of the IFG showed significant correlations in both SPM analyses of the GM volume (r2 = 0.90, p < 0.0001) and CBF (r2 = 0.88, p < 0.0001). The voxel-wise analyses revealed the brain regions, mainly the IFG, that showed hypoperfusion and atrophy related to dopaminergic loss, which suggests that the progression of dopaminergic neurodegeneration leads to regional cortical dysfunction in PD.

Periodic limb movements in sleep are linked to decreased hippocampus and amygdala volumes in the population-based BiDirect Study.

Even though numerous studies indicate that sleep disorders are associated with altered brain morphology, MRI studies focusing on periodic limb movements in sleep (PLMS) are scarce. Our aim was to investigate the association of PLMS with global and regional gray matter volumes as well as white matter hyperintensity (WMH) volume. One hundred and eighty-nine subjects (57.0 ± 7.8 years, women: 50.5%) of the population-based BiDirect Study underwent a single-night polysomnography (PSG). Standard criteria of the American Academy of Sleep Medicine were applied to evaluate sleep characteristics and calculate the PLMS index (PLMSI). T1w and FLAIR images were acquired with cerebral MRI at 3 Tesla. Voxel-based morphometry was performed to determine the total gray matter volume as well as the volume of cortical segments and subcortical gray matter areas using SPM12 and CAT12. The WMH volume was quantified with the Brain Intensity AbNormality Classification Algorithm. The independent relationship between MRI markers and PLMSI was analyzed using multivariable linear regression with adjustment for age, sex, body mass index, intracranial volume, PSG scorer, PSG device, sleep apnea, and the use of antidepressants. PLMSI was not significantly related to global gray matter volume and WMH volume. However, significant inverse associations of the PLMSI with the volume of the hippocampus (left and right hemisphere) and left amygdala were observed. A significant relationship between a higher PLMSI and lower volumes of the hippocampus and amygdala was found among the participants of the BiDirect Study. Since these associations are based on exploratory analyses, further replications are required before drawing firm conclusions.

Brain volume in Tanzanian children with sickle cell anaemia: Aneuroimaging study.

Brain injury is a common complication of sickle cell anaemia (SCA). White matter (WM) and cortical and subcortical grey matter (GM), structures may have reduced volume in patients with SCA. This study focuses on whether silent cerebral infarction (SCI), vasculopathy or anaemia affects WM and regional GM volumes in children living in Africa. Children with SCA (n=144; aged 5-20 years; 74 male) and sibling controls (n=53; aged 5-17 years; 29 male) underwent magnetic resonance imaging. Effects of SCI (n=37), vasculopathy (n=15), and haemoglobin were assessed. Compared with controls, after adjusting for age, sex and intracranial volume, patients with SCA had smaller volumes for WM and cortical, subcortical and total GM, as well as bilateral cerebellar cortex, globus pallidus, amygdala and right thalamus. Left globus pallidus volume was further reduced in patients with vasculopathy. Putamen and hippocampus volumes were larger in patients with SCA without SCI or vasculopathy than in controls. Significant positive effects of haemoglobin on regional GM volumes were confined to the controls. Patients with SCA generally have reduced GM volumes compared with controls, although some subcortical regions may be spared. SCI and vasculopathy may affect the trajectory of change in subcortical GM and WM volume. Brain volume in non-SCA children may be vulnerable to contemporaneous anaemia.

The influence of visual deprivation on the development of the thalamocortical network: Evidence from congenitally blind children and adults

The thalamus is heavily involved in relaying sensory signals to the cerebral cortex. A relevant issue is how the deprivation of congenital visual sensory information modulates the development of the thalamocortical network. The answer is unclear because previous studies on this topic did not investigate network development, structure-function combinations, and cognition-related behaviors in the same study. To overcome these limitations, we recruited 30 congenitally blind subjects (8 children, 22 adults) and 31 sighted subjects (10 children, 21 adults), and conducted multiple analyses [i.e., gray matter volume (GMV) analysis using the voxel-based morphometry (VBM) method, resting-state functional connectivity (FC), and brain-behavior correlation]. We found that congenital blindness elicited significant changes in the development of GMV in visual and somatosensory thalamic regions. Blindness also resulted in significant changes in the development of FC between somatosensory thalamic regions and visual cortical regions as well as advanced information processing regions. Moreover, the somatosensory thalamic regions and their FCs with visual cortical regions were reorganized to process high-level tactile language information in blind individuals. These findings provide a refined understanding of the neuroanatomical and functional plasticity of the thalamocortical network.

Brain cortical alterations in COVID-19 patients with neurological symptoms.

Growing evidence suggests that the central nervous system is affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), since infected patients suffer from acute and long-term neurological sequelae. Nevertheless, it is currently unknown whether the virus affects the brain cortex. The purpose of this study was to assess the cortical gray matter volume, the cortical thickness, and the cortical surface area in a group of SARS-CoV-2 infected patients with neurological symptoms compared to healthy control subjects. Additionally, we analyzed the cortical features and the association with inflammatory biomarkers in the cerebrospinal fluid (CSF) and plasma. Thirty-three patients were selected from a prospective cross-sectional study cohort during the ongoing pandemic (August 2020-April 2021) at the university hospitals of Basel and Zurich (Switzerland). The group included patients with different neurological symptom severity (Class I: nearly asymptomatic/mild symptoms, II: moderate symptoms, III: severe symptoms). Thirty-three healthy age and sex-matched subjects that underwent the same MRI protocol served as controls. For each anatomical T1w MPRAGE image, regional cortical gray matter volume, thickness, and surface area were computed with FreeSurfer. Using a linear regression model, cortical measures were compared between groups (patients vs. controls; Class I vs. II-III), with age, sex, MRI magnetic field strength, and total intracranial volume/mean thickness/total surface area as covariates. In a subgroup of patients, the association between cortical features and clinical parameters was assessed using partial correlation adjusting for the same covariates. P-values were corrected using a false discovery rate (FDR). Our findings revealed a lower cortical volume in COVID-19 patients' orbitofrontal, frontal, and cingulate regions than in controls (p < 0.05). Regional gray matter volume and thickness decreases were negatively associated with CSF total protein levels, the CSF/blood-albumin ratio, and CSF EN-RAGE levels. Our data suggest that viral-triggered inflammation leads to neurotoxic damage in some cortical areas during the acute phase of a COVID-19 infection in patients with neurological symptoms.

Alterations of gray and white matter volumes and cortical thickness in treated HIV-positive patients

Brain structural changes in HIV identified by voxel-based morphometry (VBM) alone could arise from a variety of causes that are difficult to distinguish without further information, such as cortical thickness (CT), gyrification index (GI) or sulcal depth (SD). Hence, our goal was to assess these additional metrics in HIV using high-resolution 3D T1-weighted images and investigate if surface-based morphometric (SBM) analysis would reveal significant changes in the gray matter (GM) and white matter (WM) volumes combined with alterations in cortical thickness (CT), gyrification index (GI), sulcal depth (SD). T1-w magnetization-prepared-rapid-acquisition gradient-echo (MP-RAGE) scans were acquired in 27 HIV-infected individuals on antiretroviral therapy (ART) and 15 HIV-uninfected healthy controls using a 3T MRI scanner equipped with a 16-channel head “receive” and a quadrature body “transmit” coil. Voxel-based and surface-based morphometric analyses were performed using the MATLAB based SPM Computational Anatomy Toolbox (CAT12.7(1700)). HIV-infected patients showed significantly altered GM and WM volumes, CT, GI, and SD, in multiple brain regions. This study showed the association of altered GM and WM volumes in local brain regions with the changes in region-wise CT, GI and SD measures of HIV-infected patients, especially in the parahippocampal and middle frontal regions as compared to uninfected healthy controls. The outcome of this study suggests that the findings of VBM may not necessarily indicate the volumetric shrinkage or increase alone, but might also be due to altered CT, GI, or SD. Correlation analysis showed a significantly accelerated gray matter loss with age in HIV-infected individuals compared to uninfected healthy controls.

Sex Differences in the Correlation between Fatigue Perception and Regional Gray Matter Volume in Healthy Adults: A Large-Scale Study.

The relationship between fatigue perception and regional gray matter volume (rGMV) has seldom been studied in healthy adults. Therefore, this study aimed to analyze sex differences in the correlation between rGMV and fatigue perception using Chalder’s fatigue questionnaire (CFQ). The CFQ was used to analyze the sexual features of rGMV related to the degree of perceived fatigue in 2955 healthy adults (male = 1560, female = 1395) of various ages (20–89 years, median 56). A higher CFQ score denotes a higher perceived fatigue level by the participant. According to the CFQ scores in males, the volumes of the right orbital part of the inferior frontal gyrus and left precuneus were negatively correlated (i.e., smaller rGMV had a higher CFQ score), whereas the left angular gyrus was positively correlated. In females, the right inferior temporal gyrus was negative, whereas the left middle temporal gyrus and right putamen were positive (i.e., larger rGMV had a higher CFQ score). The lack of identified regions in this large-scale study between males and females might be related to sex differences in clinical or pathological fatigue morbidities. Additionally, the sex differences in the negative or positive correlations between rGMV and fatigue perception may contribute to a better understanding of the neuronal mechanism in the early stages of fatigue development.

Regional gray matter volume mediates the relationship between neuroticism and depressed emotion.

The underlying psychological mechanism of the effect of neuroticism on depressed emotion has been widely studied. However, the neural mechanism of this relationship remains unclear. Therefore, the present study aimed to apply voxel-based morphometry (VBM) to explore the neural mechanism of the relationship between depressed emotion and neuroticism in healthy and young participants through longitudinal tracking research. The behavioral results showed that neuroticism was positively related to depressed emotion at T1 and T2 (6 months later). The VBM analysis revealed that neuroticism positively associated with the gray matter volume (GMV) in the dorsal medial prefrontal cortex (dmPFC). Mediation analysis was conducted to investigate the neural basis of the association between depressed emotion and neuroticism. The mediation result revealed that GMV of the dmPFC partially mediates the relationship between neuroticism and depressed emotion at T1 but not T2. Together, these findings suggest that the gray matter volume of dmPFC could may affect the relationship between depressed emotion and neuroticism.

Brain Anatomy Alterations and Mental Health Challenges Correlate to Email Addiction Tendency.

Despite the widespread use of email, our knowledge regarding the consequences of email addiction is lacking. The purpose of this study was to develop an email addiction tendency scale to evaluate its correlation to behavior and brain structure. Following this, the validity and reliability of the developed scale was investigated. We used voxel-based morphometry, correlation, and univariate regression analysis to assess the relationships between email addiction tendency scores and regional gray and white matter volumes, depression, and nonverbal reasoning abilities in a large sample of healthy young adults (n = 1152; mean age, 20.69 ± 1.84 years). The content validity ratio, content validity index, principal component analysis, and confirmatory factorial analysis all showed that the email addiction tendency scale (EATS) has high validity. Additionally, the Cronbach’s alpha internal consistency and split-half reliability coefficient showed that the EATS has high reliability. We found that email addiction tendency scores were significantly negatively correlated with nonverbal reasoning. We also observed that the email addiction tendency scores were significantly and positively correlated with depression symptom severity and gray matter volume of the left rostrolateral prefrontal cortex (RLPC) in subjects. These results indicate that email addiction tendency is associated with lower mental health outcomes and increased GMV in the left RLPC.

Differential Relationships Among C-Reactive Protein, Attention Functioning, and Brain Structure in Bipolar Offspring With and Without Subthreshold Mood Symptoms.

Background: Bipolar disorder (BD) is a highly heritable mood disorder. Activated low-grade inflammation may not only play an adverse role in the pathophysiology of BD, but also contribute to a resilience process. The neuroinflammatory processes may underlie the attention deficit and alteration of gray matter volume (GMV) in the early stage and premorbid period of BD. Also, the differential inflammation-brain relationship may be identified as biological markers for BD pathology or resilience.Methods: The present data were collected between March 2013 and June 2016. Sixty-four offspring of BD patients were recruited and subdivided into asymptomatic (n = 33, mean age = 17.8 years) and symptomatic (n = 31, mean age = 16.2 years) groups according to whether they manifested subthreshold mood symptoms. The diagnosis of BD was confirmed according to DSM-IV criteria. C-reactive protein (CRP) level, attention functioning, and GMV data were measured by ELISA, the Continuous Performance Test-Identical Pair test (CPT-IP), and 3.0 T magnetic resonance imaging, respectively. Their relationships were examined with mediation and moderation analyses.Results: We observed a higher level of CRP and poorer attention in the symptomatic group than the asymptomatic group and found a significant group × CRP interactive effect on GMV in regions spanning right precentral and postcentral gyri (P = .043). CRP levels negatively mediated the relationship between the group and CPT-IP scores, and the group marginally moderated the relationship between pre/postcentral gyri volumes and CPT-IP scores (P = .05).Conclusions: Symptomatic and asymptomatic bipolar offspring manifested differential inflammation-GMV-attention relationships, which may represent, respectively, an endophenotype or a resilience process for BD.

Metabolic syndrome predictors of brain gray matter volume in an age-stratified community sample of 776 Mexican- American adults: Results from the genetics of brain structure image archive.

IntroductionThis project aimed to investigate the association between biometric components of metabolic syndrome (MetS) with gray matter volume (GMV) obtained with magnetic resonance imaging (MRI) from a large cohort of community-based adults (n = 776) subdivided by age and sex and employing brain regions of interest defined previously as the “Neural Signature of MetS” (NS-MetS).MethodsLipid profiles, biometrics, and regional brain GMV were obtained from the Genetics of Brain Structure (GOBS) image archive. Participants underwent T1-weighted MR imaging. MetS components (waist circumference, fasting plasma glucose, triglycerides, HDL cholesterol, and blood pressure) were defined using the National Cholesterol Education Program Adult Treatment Panel III. Subjects were grouped by age: early adult (18–25 years), young adult (26–45 years), and middle-aged adult (46–65 years). Linear regression modeling was used to investigate associations between MetS components and GMV in five brain regions comprising the NS-MetS: cerebellum, brainstem, orbitofrontal cortex, right insular/limbic cluster and caudate.ResultsIn both men and women of each age group, waist circumference was the single component most strongly correlated with decreased GMV across all NS-MetS regions. The brain region most strongly correlated to all MetS components was the posterior cerebellum.ConclusionThe posterior cerebellum emerged as the region most significantly associated with MetS individual components, as the only region to show decreased GMV in young adults, and the region with the greatest variance between men and women. We propose that future studies investigating neurological effects of MetS and its comorbidities—namely diabetes and obesity—should consider the NS-MetS and the differential effects of age and sex.

Prefrontal cortex and putamen grey matter alterations in cannabis and tobacco users.

Previous magnetic resonance imaging studies in regular cannabis users report altered grey matter volume (GMV) in brain regions, including the prefrontal cortex (PFC), putamen and hippocampus. However, most studies have tended to recruit recreational users with high levels of cannabis use, and have not controlled for the possible confounding effects of tobacco use. We attempt to address these limitations in the present study. We acquired volumetric images in sex, age and IQ-matched groups of (1) regular Cannabis users who also smoke Tobacco cigarettes ('CT'; n = 33), (2) non-cannabis-using Tobacco cigarette smokers ('T'; n = 19) and (3) non-cannabis/tobacco-using Controls ('C'; n = 35). GMV in bilateral PFC, putamen and hippocampal regions was compared across groups. We also examined the associations between GMV differences and levels of cannabis and tobacco use, measures of intellectual function, and of depression, anxiety and stress. Relative to controls, both CT and T groups showed lower GMV in the left inferior frontal gyrus, and greater GMV in the putamen. In addition, lower GMV in the right frontal pole in the CT group (but not the T group) was associated with lifetime cannabis use, but not with cigarette use. Regular cannabis users who also smoked tobacco cigarettes showed altered GMV patterns relative to controls. However, a similar pattern of GMV differences was also seen between regular tobacco users that did not use cannabis. Further research is needed to disentangle the effects of cannabis and tobacco use on brain structure.

Cerebral gray matter volume correlates with fatigue and varies between desk workers and non-desk workers.

Chronic fatigue syndrome (CFS), a clinical entity of chronic fatigue, has been associated with a decrease in regional gray matter volume (rGMV). In this study targeting a large number of healthy middle-aged individuals without CFS, the relationship between fatigue perception and rGMV was investigated. Considering that the work setting is an environmental factor that influences fatigue perception among healthy individuals, the differences between desk workers and non-desk workers were investigated. Chalder Fatigue Questionnaire (CFQ) scores were used for perceptional evaluation of fatigue, and rGMV of 110 brain regions was adapted with Statistical Parametric Mapping (SPM) 8 on 1.5 T magnetic resonance imaging (MRI) results for the volumetric calculation of gray matter. The CFQ scores were negatively correlated with the right supplementary motor area (SMC) and positively correlated with the right superior parietal lobule (SPL) and left basal forebrain in all participants (n = 1,618). In desk workers and non-desk workers, the CFQ scores correlated with different regions and yielded different mechanisms of fatigue perception in the brain. Identifying the gray matter regions correlated with fatigue perception in healthy individuals may help understand the early stage of fatigue progression and establish future preventive measures.

Association of body mass index and its classifications with gray matter volume in individuals with a wide range of body mass index group: A whole-brain magnetic resonance imaging study.

AimTo examine the association of body mass index (BMI) [kg/m2] and its classifications (underweight [BMI < 18.5], normal [18.5 ≤ BMI < 25], overweight [25 ≤ BMI < 30], and obese [BMI ≥ 30]) with brain structure in individuals with a wide range of BMI group.Materials and methodsThe participants included 382 right-handed individuals (mean age: 46.9 ± 14.3 years, 142 men and 240 women). The intelligence quotient was assessed using the Japanese Adult Reading Test. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to analyze the association of BMI and its classifications with gray and white matter structures, respectively.ResultsAccording to VBM, BMI was significantly and negatively correlated with the bilateral cerebellum exterior volumes. In group comparisons, the right cerebellum exterior volume was significantly lower in the overweight or obese group than in the underweight or normal group, while the bilateral cuneus and calcarine cortex, left cuneus, and left precuneus volume was significantly lower in the underweight group than in the non-underweight group. Sex-related stratification analyses for VBM revealed that BMI was significantly and negatively correlated with the bilateral cerebellum exterior volumes only in women. In group comparisons, the left cerebellum exterior volume was significantly lower in obese women than in non-obese women. The left thalamus proper and the right cerebellum exterior volumes were significantly lower in overweight or obese group than in underweight or normal group in men and women, respectively. The bilateral cuneus and calcarine cortex, left cuneus and carcarine cortex, and bilateral cuneus volume was significantly lower in underweight men than in non-underweight men. In contrast, there were no notable findings on DTI.ConclusionOur results suggest association of continuous BMI, being overweight or obese, and being underweight with decreased gray matter volume in individuals with a wide range of BMI group. Furthermore, sex-related differences are seen in the association of BMI and its classifications with regional gray matter volume reductions. Abnormally high or low BMIs may have a negative influence on regional gray matter volumes.

Distinct brain structural abnormalities in attention-deficit/hyperactivity disorder and substance use disorders: A comparative meta-analysis

As two common mental disorders during the period of adolescence that extend to early adulthood, attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) have considerable diagnostic co-occurrence and shared neuropsychological impairments. Our study aimed to identify overlapping and distinct brain structural abnormalities associated with ADHD and SUDs among adolescents and young adults. A systematic literature search on voxel-based morphometry (VBM) studies of ADHD and SUDs was conducted in PubMed and Web of Science. Data were extracted and analyzed to identify brain abnormalities using Seed-based d-Mapping software. Data-driven functional decoding was conducted to identify the psychophysiological functioning associated with brain alterations. 13 and 14 VBM studies for ADHD (619 patients and 483 controls) and SUDs (516 patients and 413 controls), respectively, were included. Patterns of decreased gray matter volume (GMV) were found in the left precentral gyrus, bilateral superior frontal gyri, and left inferior frontal gyrus in the ADHD group compared to the control group. In contrast, individuals with SUDs, relative to controls, were characterized by increased GMV in the left putamen and insula. Comparative analysis indicated larger regional GMV in the right inferior parietal lobule and smaller volumes in the left putamen and left precentral gyrus in the ADHD group than in the SUDs group. Dissociable brain structural abnormalities in adolescents and young adults with ADHD and SUDs potentially implicate different pathogeneses and provide a reference for differential diagnosis and early detection for shared symptomology and comorbidity.

Regional gray matter volume correlates to physical and mental fatigue in healthy middle-aged adults

Previous studies on neural/molecular mechanisms of fatigue focused on a variety of brain functions, morphological changes, and neurochemical functions such as neurotransmitter and neuroimmune dynamics. However, MRI morphological changes were adopted primarily to compare patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and healthy controls. A few studies have been done on healthy subjects with fatigue scores; one study with 63 adults (their ages of 53.2 ± 8.3) showed the gray matter volume (GMV) reduction in good correlation with a higher score of fatigue. The other one with university students (their ages of 20.7 ± 1.8) demonstrated no significant correlation between regional GMV (rGMV) and fatigue severity. To elucidate the brain structural underpinning in parallel with fatigue development, a large number of healthy middle-aged adults (n = 1873; aged 54.1 ± 5.4) without ME/CFS were recruited, and the correlation between both rGMV in the cerebrum including basal ganglia and Chalder's fatigue questionnaire (CFQ) with physical and mental categories were investigated. A higher CFQ score denotes a higher perceived fatigue level by the participant. The physical fatigue scores of CFQ showed a significantly negative correlation (i.e., smaller rGMV for higher CFQ score) with the volume of the right planum temporale and supplemental motor cortex (SMC), while the left putamen, middle temporal gyrus (MTG), parietal operculum, and right precentral gyrus showed a significantly positive correlation (i.e., bigger rGMV for higher CFQ score). In the mental fatigue scores, the right SMC and left lateral orbital gyrus (LOG) showed a significantly negative correlation, while only the left fusiform gyrus showed a significantly positive correlation. In total scores of (both physical and mental) fatigue, the right SMC and orbital part of the inferior frontal gyrus (OIFG) showed a negative correlation, while the left putamen and MTG showed a positive correlation. Therefore, the right SMC may play a critical role in fatigue progression because of the only common factor among physical, mental, and total fatigue. The left putamen may play a compensatory role with a positive correlation to physical and total fatigue. Additionally, identifying the other gray matter regions that positively or negatively correlated to CFQ of healthy adults may help deepen the understanding of early-stage fatigue progression, leading to the future establishment of preventive measures through volumetrics by using MRI.

A Multimodal Neuroimaging and Neuropsychological Study of Visual Hallucinations in Alzheimer's Disease.

Hallucinations in Alzheimer's disease (AD) have been linked to more severe cognitive and functional decline. However, research on visual hallucinations (VH), the most common type of hallucinations in AD, is limited. To investigate the cognitive and cerebral macrostructural and metabolic features associated with VH in AD. Twenty-four AD patients with VH, 24 with no VH (NVH), and 24 cognitively normal (CN) matched controls were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Differences in regional gray matter (GM) volumes and cognitive performance were investigated with whole brain voxel-based morphometry analyses of MRI structural brain scans, and analyses of neuropsychological tests. Glucose metabolic changes were explored in a sub-sample of patients who had FDG-PET scans available. More severe visuoconstructive and attentional deficits were found in AD VH compared with NVH. GM atrophy and hypometabolism were detected in occipital and temporal areas in VH patients in comparison with CN. On the other hand, NVH patients had atrophy and hypometabolism mainly in temporal areas. No differences in GM volume and glucose metabolism were found in the direct comparison between AD VH and NVH. In addition to the pattern of brain abnormalities typical of AD, occipital alterations were observed in patients with VH compared with CN. More severe visuoconstructive and attentional deficits were found in AD VH when directly compared with NVH, and might contribute to the emergence of VH in AD.

Early gray matter atrophy and neurological deficits in patients with carbon monoxide poisoning.

To investigate early neurological deficits-related change patterns in gray matter (GM) volume in patients with carbon monoxide poisoning (COP) and GM volume differences between patients with and without delayed neurological sequelae (DNS) and those with and without T2 hyperintense lesions after COP. Forty-one COP patients (24 patients with DNS) and 36 sex- and age-matched healthy controls (HC) were enrolled in this study. The neurological assessments were administered within 24h after MRI scans. Voxel-based morphometry analysis was used to detect regional GM volume change. The COP group had statistically significant GM atrophy in the bilateral prefrontal and temporal lobes, anterior cingulate (ACC), thalamus, posterior cerebellum, and right hippocampus compared to the HC group. Atrophy in the left medial orbital superior frontal gyrus (SFG), bilateral ACC, and bilateral thalamus were related to lower Mini-Mental State Examination (MMSE) scores and higher Unified Parkinson's Disease Rating Scale subsection III and neuro-psychiatric inventory scores. Atrophy in the hippocampus and posterior cerebellum were also related to decrease MMSE scores. The DNS subgroup had greater GM atrophy in the limbic system than the non-DNS subgroup. Compared to the subgroup without T2 hyperintense lesions, greater GM atrophy in the limbic system, motor and visual cortex, and default network was observed in the subgroup with T2 hyperintense lesions. GM atrophy in the medial orbital SFG, ACC, thalamus, hippocampus, and posterior cerebellum is associated with early neurological deficits in patients with COP. Greater atrophy occurred in patients with DNS and those with T2 hyperintense lesions.